A PARTIALLY ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS INDUCES HOST IMMUNITY THAT CORRELATES WITH RESISTANCE TO PATHOGENIC VIRUS CHALLENGE

Three infectious, attenuated molecular clones of simian immunodeficien cy virus (SIVmac) were tested for viral and host determinants of prote ctive immunity. The viruses differed in degree of virulence from highl y attenuated to moderately attenuated to partially attenuated. Levels of immune stimulation and antiviral immunity were measured in rhesus m acaques inoculated 2 years previously with these viruses. Monkeys infe cted with the highly attenuated or moderately attenuated viruses had m inimal lymphoid hyperplasia, normal CD4/CD8 ratios, low levels of SIV- specific antibodies, and cytotoxic T-lymphocyte activity against p55(g ag) (Gag) or gp160(env) (Env). Monkeys infected with the partially att enuated virus had moderate to marked lymphoid hyperplasia, normal CD4/ CD8 ratios, high levels of SN-specific antibodies, and cytotoxic T-lym phocyte activity against both Gag and Env. After pathogenic virus chal lenge, monkeys immunized with the partially attenuated virus had 100- to 1,000-fold-lower viral load in peripheral blood mononuclear cells a nd lymph node mononuclear cells than naive control animals. One of fou r monkeys immunized with the highly attenuated virus and two of four m onkeys immunized with the moderately attenuated virus developed simila rly low viral loads after challenge. These three attenuated strains of SIV induced a spectrum of antiviral immunity that was inversely assoc iated with their degree of attenuation. Only the least attenuated viru s induced resistance to challenge infection in all immunized monkeys.